Expression of three zebrafish orthologs of human FMR1-related genes and their phylogenetic relationships

Abstract

The human fragile X mental retardation syndrome is caused by expansions of a CGG repeat in the FMR1 gene. FXR1 and FXR2 are autosomal paralogs of FMR1. The products of the three genes, FMRP, FXR1P, and FXR2P, respectively, belong to a family of RNA-binding proteins. While the FMR1-related gene family is well described in human, mouse and Drosophila, little is known about zebrafish (Danio rerio) orthologs of these genes. Here we collate the known FMR1-related gene sequences from zebrafish, examine their regions of structural conservation, and define their orthologies with the human genes. We demonstrate that zebrafish possess only three FMR1-related genes, fmr1, fxr1 and fxr2, and these are orthologous to the human FMR1, FXR1 and FXR2 genes respectively. We examine the spatiotemporal pattern of transcription of the zebrafish genes from 0 hours post fertilisation (hpf) until 24 hpf. Expression of fmr1, fxr1 and fxr2 is widespread throughout this time. However, relative to surrounding tissues, expression of fxr2 is raised in adaxial and somitic cells by 12 hpf while fxr1 expression is high in the anterior of the embryo, and is raised in adaxial cells by 12 hpf. Distinct patterns (and levels) of expression are seen for the different genes later in development. At 24 hpf, fxr1 and fxr2 transcripts show complex distribution patterns in somites. The expression of the FMR1-related gene family in zebrafish tissues is broadly consistent with expression in mouse and human, supporting the idea that zebrafish should be an excellent model organism in which to study the functions of the vertebrate FMR1-related gene family.

First in vivo evidence of microRNA-induced fragile X mental retardation syndrome

“…Like human, zebrafish possesses three FMRP-related genes, fmr1, fxr1 and fxr2, which are orthologous to the human FMR1, FXR1 and FXR2 genes, respectively. 6 The expression patterns of these FMRP-familial genes in zebrafish tissues are broadly consistent with those in mouse and human, suggesting that such a loss-of-fmr1-function zebrafish is an excellent model organism for studying the FraX etiology. 6 We constructed the anti-fmr1 miRNA transgene based on a proof-of-principle design of the artificial SpRNAi-rGFP transgene as previously re- Figure 1 Morphological changes of lateral pallium neurons in the loss-of-fmr1-function zebrafish.…”

“…6 The expression patterns of these FMRP-familial genes in zebrafish tissues are broadly consistent with those in mouse and human, suggesting that such a loss-of-fmr1-function zebrafish is an excellent model organism for studying the FraX etiology. 6 We constructed the anti-fmr1 miRNA transgene based on a proof-of-principle design of the artificial SpRNAi-rGFP transgene as previously re- Figure 1 Morphological changes of lateral pallium neurons in the loss-of-fmr1-function zebrafish. Because the whole Tg(UAS:gfp) zebrafish tissues expresses green GFP and the anti-fmr1 miRNA transgene is marked with red GFP, we can easily observe the normal dendritic neurons (green) versus the loss-of-fmr1-function neurons (yellow).…”

Modeling fragile X syndrome in the <i>Fmr1</i> knockout mouse

“…Animal models of FXS have been developed in various species, such as the Drosophila fruit fly, zebrafish, mouse, and rat (44)(45)(46)(47)(48). Much effort has focused on the characterization of mouse models of FXS, in particular the Fmr1 knockout (KO) mouse.…”

Repeat-Associated MicroRNAs Trigger Fragile X Mental Retardation-Like Syndrome in Zebrafish~!2008-10-29~!2008-11-12~!2008-11-26~!

“…They possess three FMR1-related familial genes, fmr1, fxr1 and fxr2, which are orthologous to the human FMR1, FXR1 and FXR2 genes, respectively [10]. The tissue expression patterns of these familial genes in zebrafish are broadly consistent with those of humans [10,11]. As shown in Fig.…”

“…Zebrafish (Danio rerio) have served as an excellent model for studying human mental disorders, including FXS and autism [9]. They possess three FMR1-related familial genes, fmr1, fxr1 and fxr2, which are orthologous to the human FMR1, FXR1 and FXR2 genes, respectively [10]. The tissue expression patterns of these familial genes in zebrafish are broadly consistent with those of humans [10,11].…”